Satoshi Tanabe

A multicenter retrospective study of endoscopic resection for early gastric cancer.

BackgroundThe reported outcomes of endoscopic resection (ER) for early gastric cancer (EGC) remain limited to several single-institution studies.MethodsA multicenter retrospective study was conducted at 11 Japanese institutions concerning their results for ER, including conventional endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).ResultsA total of 714 EGCs (EMR, 411; ESD, 303) in 655 consecutive patients were treated from January to December 2001. Technically, 511 of the 714 (71.6%) lesions were resected in one piece. The rate of one-piece resection with ESD (92.7%; 281/303) was significantly higher compared with that for EMR (56.0%; 230/411). Histologically, curative resection was found in 474 (66.3%) lesions. The rate of curative resection with ESD (73.6%; 223/303) was significantly higher compared with that for EMR (61.1%; 251/411). Blood transfusion because of bleeding was required in only 1 patient (0.1%) with EMR of 714 lesions. Perforation was found in 16 (2.2%). The incidence of perforation with ESD (3.6%; 11/303) was significantly higher than that with EMR (1.2%; 5/411). All complications were managed endoscopically, and there was no procedure-related mortality. The median follow-up period was 3.2 years (range, 0.5–5.0 years). In total, the 3-year cumulative residual-free/recurrence-free rate and the 3-year overall survival rate were 94.4% and 99.2%, respectively. The 3-year cumulative residual-free/recurrence-free rate in the ESD group (97.6%) was significantly higher than that in the EMR group (92.5%).ConclusionER leads to an excellent 3-year survival in clinical practice and could be a possible standard treatment for EGC. ESD has the advantage of achieving one-piece resection and reducing local residual or recurrent tumor.

Clinical outcome of endoscopic aspiration mucosectomy for early stage gastric cancer

BACKGROUND Endoscopic mucosal resection is an established treatment option for early stage gastric cancer. However, several problems with endoscopic mucosal resection remain to be solved, such as appropriate treatment for recurrence and incomplete tumor resection. The outcome for patients undergoing endoscopic aspiration mucosectomy (endoscopic mucosal resection) by a modification of the cap-fitted technique was evaluated retrospectively to determine factors associated with complete resection and tumor recurrence. METHODS Endoscopic mucosal resection was performed in 106 patients with early stage gastric cancers up to 20 mm in diameter that were well or moderately differentiated adenocarcinoma. All were superficial lesions without ulceration, distinct signs of submucosal invasion, or a poorly demarcated border. En bloc (tumors <10 mm in diameter) or piecemeal (tumors 10-20 mm in diameter) resection was performed. Follow-up endoscopy was performed at 2, 6, 12, 18, and 24 months and thereafter once per year. Outcome and factors associated with complete resection and tumor recurrence were assessed retrospectively. RESULTS Sixty-eight patients (64%) underwent en bloc resection and 38 (36%) piecemeal resection. The mean longest dimension (SD) of the resected lesions was significantly greater after piecemeal resection (12.3 [4.0] mm) than after en bloc resection (7.6 [4.0] mm; p < 0.01). In patients with tumors completely resected, there was no recurrence after either en bloc or piecemeal resection. Six of 8 patients found to have submucosal invasion after endoscopic mucosal resection underwent surgery. Patients with incompletely resected intramucosal lesions underwent additional endoscopic treatment. Cancer recurred in 3 patients (2.8%), all of whom had lesions measuring more than 15 mm in diameter. CONCLUSIONS Endoscopic mucosal resection is safe and useful for the management of early stage gastric cancer. Further improvement in outcome requires more accurate preoperative diagnosis and postoperative histopathologic evaluation. Patients with incompletely resected lesions should undergo aggressive additional treatment.

Usefulness of endoscopic aspiration mucosectomy as compared with strip biopsy for the treatment of gastric mucosal cancer

BACKGROUND Several techniques are available for the endoscopic treatment of gastric intramucosal cancers, but their advantages and disadvantages have not been adequately evaluated. We compared the therapeutic usefulness of endoscopic aspiration mucosectomy with that of strip biopsy. METHODS Between May 1995 and May 1997, we performed strip biopsy (May 1995 through February 1996) or endoscopic aspiration mucosectomy (March 1996 through May 1997) in a consecutive series of patients with intestinal-type intramucosal cancer. Parameters of assessment included the following: size of removed specimens, en bloc resection rate, time required for resection, duration of hospitalization, and complications. RESULTS Forty-nine patients with gastric intramucosal cancers underwent endoscopic aspiration mucosectomy and 44 underwent strip biopsy. The two groups were similar with respect to age, gender, and lesion macroscopic appearance, size, and site. The mean longest diameter of the resected specimens was significantly greater with endoscopic aspiration mucosectomy (20.3 +/- 3.4 mm) than with strip biopsy (15. 8 +/- 4.4 mm) (p < 0.001). The rate of en bloc resection (resection of an entire lesion in one procedure) was significantly higher with endoscopic aspiration mucosectomy (61.2%, 30 of 49) than with strip biopsy (36.4%, 16 of 44) (p < 0.05). The number of specimens obtained by piecemeal resection was slightly, but not significantly, higher with strip biopsy (2.4 +/- 1.7) than with endoscopic aspiration mucosectomy (2.0 +/- 1.7). The time required for treatment was similar for each procedure. The duration of hospitalization was significantly shorter with endoscopic aspiration mucosectomy (12.8 +/- 5.3 days) than with strip biopsy (15.9 +/- 74 days) (p < 0.05). As for complications, the rate of bleeding was 20. 5% (9 of 44) with strip biopsy and 10.2% (5 of 49) with endoscopic aspiration mucosectomy; bleeding was controlled in all cases by treatment with a heater probe. CONCLUSIONS Endoscopic resection of large gastric intramucosal tumors is easier with endoscopic aspiration mucosectomy compared with strip biopsy. Endoscopic aspiration mucosectomy is a useful procedure for en bloc resection.

Mixed-histologic-type submucosal invasive gastric cancer as a risk factor for lymph node metastasis: feasibility of endoscopic submucosal dissection

BACKGROUND AND STUDY AIMS The clinicopathologic features of gastric cancers containing a mixture of differentiated-type and undifferentiated-type components remain uninvestigated. We evaluated the risk of lymph node metastasis and the feasibility of endoscopic submucosal dissection (ESD) for the treatment of mixed-histologic-type gastric cancers. PATIENT AND METHODS We histologically classified 376 cases of gastric cancer with submucosal invasion into four types (differentiated type, differentiated-type-predominant mixed type, undifferentiated-type-predominant mixed type, and undifferentiated type) and studied the clinicopathologic relations of each type to lymph node metastasis. Lymphatic invasion was evaluated by D2-40 immunostaining. RESULTS The overall prevalence of lymph node metastasis in gastric cancer with submucosal invasion was 16.5% (62/376). The prevalence of lymph node metastasis was 36.5% (23/63) in undifferentiated-type-predominant mixed type, which was significantly higher than those in the other three types (P < 0.001 vs. differentiated type, P = 0.013 vs. differentiated-type-predominant mixed type, and P = 0.003 vs. undifferentiated type). Lymphatic invasion, a depth of invasion of 500 microm or more from the lower margin of the muscularis mucosae (SM2), tumor size above 30 mm, and undifferentiated-type-predominant mixed histologic type were independent risk factors for lymph node metastasis. Submucosal cancers without these four risk factors were free of lymph node metastasis (0/41; 95 % confidence interval 0%-8.6%). CONCLUSIONS Undifferentiated-type-predominant mixed-type gastric cancer with submucosal invasion carries a high risk of lymph node metastasis. ESD can be indicated for gastric cancer with submucosal invasion provided that the following conditions indicating a low risk of metastasis are met: a depth of invasion of no more than 500 microm or more from the lower margin of the muscularis mucosae (SM1), no lymphatic invasion, a tumor size of no more than 30 mm, and a proportion of undifferentiated components below 50%.

Narrow band imaging for detecting superficial squamous cell carcinoma of the head and neck in patients with esophageal squamous cell carcinoma

BACKGROUND AND STUDY AIMS Narrow band imaging combined with magnifying endoscopy (NBI-ME) is useful for the detection of superficial squamous cell carcinoma (SCC) within the oropharynx, hypopharynx, and oral cavity. The risk of a second primary SCC of the head and neck is very high in patients with esophageal SCC. This prospective study evaluated the detection rate of superficial SCC within the head and neck region (superficial SCCHN) with NBI-ME in patients with esophageal SCC. PATIENTS AND METHODS Between March 2006 and February 2008, 112 patients with a current or previous diagnosis of esophageal SCC were enrolled. All patients underwent endoscopic screening of the head and neck by NBI-ME. The primary end point was the detection rate for superficial SCCHN. Secondary end points were to compare demographic characteristics between patients with and without superficial SCCHN and to assess the clinical course of patients with superficial SCCHN. RESULTS The detection rate for superficial SCCHN was 13 % (15/112). The prevalence of multiple Lugol-voiding lesions, observed endoscopically throughout the esophageal mucosa after application of Lugol dye solution, was significantly higher in patients with superficial SCCHN than in those without (100 % vs. 24 %, P < 0.0001). Minimally invasive curative treatment with organ preservation was feasible without severe complications in patients with superficial SCCHN after curative treatment of esophageal SCC. CONCLUSIONS In patients with esophageal SCC, NBI-ME is useful for detecting superficial SCCHN, thereby facilitating minimally invasive treatment.

Narrow band imaging for detecting superficial oral squamous cell carcinoma: a report of two cases.

We present two cases of superficial squamous cell carcinoma of the floor of the mouth, which were coincidentally detected by narrow band imaging (NBI) combined with magnifying gastrointestinal endoscopy (GIE) during gastrointestinal evaluation. We successfully removed the lesions using laser assisted with NBI combined with magnifying GIE. Because NBI combined with magnifying GIE shows a well‐demarcated brownish area and scattered foci of microvascular proliferation, it may play an important role in the management of superficial squamous cell carcinoma in the oral cavity.

Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial).

PURPOSE We compared biweekly irinotecan plus cisplatin (BIRIP) with irinotecan alone as the second-line chemotherapy (SLC) for advanced gastric cancer (AGC). METHODS Patients with metastatic or recurrent gastric cancer refractory to S-1-based first-line chemotherapy were randomly assigned to receive BIRIP (irinotecan 60mg/m(2) plus cisplatin 30mg/m(2), every 2weeks) or irinotecan alone (irinotecan 150mg/m(2), every 2weeks). The primary end-point was to show the superiority of BIRIP to irinotecan in terms of progression free survival (PFS). RESULTS 130 patients were enrolled. PFS was significantly longer in the BIRIP group (3.8months [95% confidence interval (CI) 3.0-4.7]) than in the irinotecan group (2.8months [2.1-3.3]; hazard ratio 0.68, 95% CI 0.47-0.98; P=0.0398). Median overall survival was 10.7months in the BIRIP group and 10.1months in the irinotecan group (HR 1.00, 95% CI 0.69-1.44, P=0.9823). The objective response rate was 22% in the BIRIP group and 16% in the irinotecan group (P=0.4975). However, the disease control rate was significantly better in the BIRIP group (75%) than in the irinotecan group (54%, P=0.0162). The incidences of grade 3 or worse adverse events did not differ between the two groups. Any grade elevation of serum creatinine was more common in the BIRIP group (25% versus 8%, P=0.009), but any grade diarrhoea (17% versus 42%, P=0.002) was more common in the irinotecan group. CONCLUSION BIRIP significantly prolonged PFS as compared with irinotecan alone and was tolerated as SLC, but did not demonstrate the survival benefit in this trial.

A phase II study of endoscopic submucosal dissection for superficial esophageal neoplasms (KDOG 0901)

BACKGROUND Most previous studies of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms were retrospective; prospective studies are scant. OBJECTIVE To prospectively assess the efficacy and safety of ESD for superficial esophageal neoplasms. DESIGN Phase II study. SETTING University hospital. PATIENTS Fifty-two patients (median age 68 years; 48 men) who had a histologic diagnosis of superficial esophageal cancer without metastasis on CT or high-grade intraepithelial neoplasia (HGIN) were enrolled from April 2009 through November 2011. INTERVENTION ESD was used to treat 56 lesions. All procedures were done by 4 endoscopists who each had previously performed ESD in more than 100 patients with gastric tumors. MAIN OUTCOME MEASUREMENTS The primary endpoint was the R0 resection rate, and secondary endpoints were the safety and the rate of accurately diagnosing tumor depth on endoscopic examination. RESULTS The median treatment time was 69 minutes (24-168 minutes). The histopathologic diagnosis was squamous cell carcinoma in 49 lesions, HGIN in 5, and tubular adenocarcinoma in 2. The en bloc resection rate and R0 resection rate were 100% and 94.6%, respectively. The rates of adverse events during ESD and after ESD were 22.2% and 53.8%, respectively, but most events were mild. One patient (1.9%) had mediastinal emphysema without perforation. The rate of accurately diagnosing tumor depth on endoscopic examination was 76.8%. LIMITATIONS Single-center, nonrandomized study. CONCLUSION Our study showed that ESD was an effective and relatively safe treatment for superficial esophageal neoplasms. ESD may be a useful treatment option for superficial esophageal neoplasms in hospitals with endoscopists who are experts in performing ESD for gastric tumors. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000002047.).

Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer

BACKGROUND Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

Intratumoral lymphangiogenesis of esophageal squamous cell carcinoma and relationship with regulatory factors and prognosis

The clinical and pathological significance of intratumoral lymphangiogenesis (ITL) with human esophageal squamous cell carcinomas (ESCC) remains unclear, as does the role of signaling molecules such as vascular endothelial growth factor (VEGF)‐A,C, platelet‐derived growth factor (PDGF)‐A, and p53, in the regulation of ITL. Lymphatic vessel density (LVD) was significantly increased in VEGF‐A and VEGF‐C immunohistochemical score 1 and 2–3 groups as compared to the score 0 group and also with high of VEGF‐A, VEGF‐C and PDGF‐A mRNA expression. Both LVD and blood vessel density (BVD) were significantly greater in the p53 gene mutant group than in the wild‐type group. Lymph node metastasis was significantly more frequent with than without ITL and Kaplan–Meier analysis indicated a significantly poorer prognosis. Multivariate analysis using Cox proportional hazard method showed that invasion depth, lymph node metastasis and ITL were independent prognostic factors.